An enormous amount of time and effort have been spent on physiological studies of the anterior pituitary gland; however, relatively little is known about the intrahypophyseal regulatory mechanisms in this tissue. Histological and ultrastructural data suggest that homologous and heterologous cell types within the anterior pituitary gland form functional cellular associations. Data obtained in our laboratory indicate that the in vitro biological responsiveness of pituitary gonadotrophs to the hypothalamic releasing hormone LHRH is affected by the cells ability to form functional interactions with other pituitary cell types. The primary objective of this research proposal will be to determine whether hypothalamic releasing hormones alter the biological responsiveness of pituitary cells through a cyclic nucleotide dependent upregulation of intercellular communication. Exogenous cyclic nucleotides will be utilized to enhance the biological responsiveness of high density pituitary cell cultures to hypothalamic hormone stimulation. The hypothesized effect of the cycle nucleotide induced change in intercellular communication will then be evaluated by freeze-fracture electron microscopic morphometric analysis of plasma membrane gap junctions. Demonstration of hormone mediated, cyclic nucleotide dependent upregulation of intercellular communication would provide cells with a fundamental mechanism for regulating and coordinating their physiological activity within a tissue. This proposed mechanism of hormone mediated action would have important clinical ramifications during the differentiation and morphogenesis of endocrine tissues.